Parkinson Flashcards
Parkinson’s
Progressive nervous system disease Starts gradually Movement disorder ◦ Bradykinesia ◦ Muscle rigidity ◦ Resting tremors ◦ Postural instability Pathology ◦ Extensive deterioration of neurons within basal ganglia of the brain ◦ Dopamine loss ◦ Increased cholinergic activity
Therapeutic goals
◦ Ideal treatment that reverses neuronal degeneration or prevents further
degeneration does not exist
◦ The goal is to improve the patient’s ability to carry out the activities of daily life
◦ Drug selection and dosages are determined by the extent to which PD interferes
with work, dressing, eating, bathing, and other activities of daily living
Therapeutic Drug Class Alternatives
Dopaminergics Dopamine Agonists MAO B inhibitors Glutamate antagonist (amantadine) Anticholinergics Catechol‐O‐Methyltransferase
Dopaminergics - Options
◦ Levodopa (Dopar, Larodopa)
◦ Levodapa‐carbidopa(Sinemet, Sinemet DR, Madopar)
◦ Duodopa (continuous to small intestine)
Dopaminergics clinical indications
◦ Most effective for tremors and rigidity
◦ Also used: postencephalitic and PD associated with cerebral ateriosclerosis
Levadopa Pharmacokinetics and
Pharmacodynamics - Conversion
Conversion of levodopa to dopamine
◦ Restores normal balance between excitation and inhibition of neurons
◦ Carbifdopa enhances concentration of levodopa to reach brain
Absorption in gut, hampered by food
Biotransformed in liver
Short ½ life, requires frequent dosing
Renally eliminated, breast milk also.
Levadopa SE
◦ N&V most common
◦ Other: dry mouth, difficulty swallowing, worsening hand tremors, numbness, syncope, sudden sleep
Levadopa Long Term Therapy
◦ Dyskinesia, on‐off phenomenon, psychiatric manifestations, cardiac arrhythmia
Levadopa Contraindications
◦ Concurrent MAOIs, uncontrolled HTN, narrow angle glaucoma, malignant melanoma
◦ CVD, Renal, liver disease, PUD, asthma/COPD, adrenergic therapy, Pregnance Cat D, BF, children < 12
Levadopa Prescription and Monitoring
Frequency of dosing patient dependent
◦ 75mg carbidopa needed to achieve full decarboxylation
Target dose
◦ Smallest dosage necessary to control symptoms and decrease disability
Monitoring
◦ Periodic CBC, LFTs, renal studies
May interfere with urine glucose and ketone tests
Dopamine Agonists - Options
◦ Bromocriptine (Parlodel) ◦ Pergolide (Permax) ◦ Rotigotine (patch) ◦ Apomorphine (IV/IM) Ropinirole (Requip CR) ◦ Pramipexole (Mirapex)
Dopamine Agonists - Clinical Indications
◦ Idiopathic and encephalic PD, restless legs
◦ Adjunct to levodopa
◦ Cannot be discontinued abruptly
◦ Require 3x a day dosing
Dopamine Agonists - PK/PD
◦ Pramipexole no hepatic metabolism
Dopamine Agonists SE
◦ Orthostatic hypotension, GI disturbance, less dyskinesia, drowsiness, insomnia
◦ Dyspnea, angina, arrhythmias, orthostosis possible (esp. in hot environs), compulsive behaviors
Dopamine Agonists - Interacions
Pergolide
Monamine Oxidase B Inhibitors - Options
◦ Selegiline (Eldepryl)
◦ Rasegeline (Agilect, Zelipar)
◦ Safinamide
Monamine Oxidase B Inhibitors - Clinical Indications
◦ Adjunct to Levodopa
◦ Most effective early stages, early onset
Monamine Oxidase B Inhibitors - MOA
◦ Selegiline:
◦ blocks MAO‐B; neuroprotective properties?
◦ May be monotherapy; dose twice daily
◦ Amphetamine metabolites
◦ Rasegiline:
◦ Prolongs survival of dopamine neurons; neuroprotective properties?